two variants separated by one or more nucleotides should preferably be described individually and not as a “delins”

exception: two variants separated by one nucleotide, together affecting one amino acid, should be described as a “delins” (e.g. r.142_144delinsugg (p.Arg48Trp)).
NOTE: this prevents tools predicting the consequences of a variant to make conflicting and incorrect predictions of two different substitutions at one position

a “u” to “a” substitution 41 nucleotides 3’ of the translation termination codon

LRG_199t1:r.[897u>g,832_960del]

two different transcripts, 897u>g and r.832_960del, derive from one variant (LRG_199t1:c.897T>G at the DNA level)

the description r.76_77delinsug is preferred over r.[76a>u;77a>g]NOTE: based on the definition of a substitution, i.e. one nucleotide replaced by one other nucleotide, this change can not be described as a substitution like r.76_77aa>ug or r.76aa>ug

NM_004006.1:r.0

no RNA from the variant allele could be detected

LRG_199t1:r.spl

RNA has not been analysed but it is very likely that splicing is affected

LRG_199t1:r.?

an effect on the RNA level is expected but it is not possible to give a reliable prediction of the consequences (RNA not analysed)

LRG_199t1:r.85=/u>c

a mosaic case where at position 85 besides the normal sequence (a U, described as “=”) also transcripts are found containing a C (r.85u>c)

NOTE: irrespective of the frequency in which each nucleotide was found, the reference is always described first

LRG_199t1:r.85=//u>c

a chimeric case, i.e. the sample is a mix of cells containing r.85= and r.85u>c.

NOTE: irrespective of the frequency in which each nucleotide was found, the reference is always described first

Q&A

Are polymorphisms described like r.76a/g?

No, all substitutions are described as r.76a>g. In the past, the format r.76a/g has been used to describe "polymorphic" sequence variants. Note that a description should be neutral, simply describe the change, and not include any other information like predicted or known functional consequences.

Can I describe a GC to TG variant as a dinucleotide substitution (r.4gc>ug)?

No, this is not allowed. By definition a substitution changes one nucleotide into one other nucleotide. The change "ugugcca" to "uguugca" should be described as a deletion/insertion (indel) as r.4_5delinsug.

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Discussions regarding HGVS nomenclature are necessary in order to further improve them. What is listed on these pages represents the current consensus of the recommendations. We invite everybody to send us comments or examples of cases that are not yet covered, with a suggestion of how to describe these (E-mail:VarNomen @ HGVS.org).